QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 11, 2006, 26(2):467-478; doi:10.1523/JNEUROSCI.4265-05.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Szot, P. Articles by Raskind, M. A. Search for Related Content PubMed PubMed Citation Articles by Szot, P. Articles by Raskind, M. A.

 Previous Article  |  Next Article 

Neurobiology of Disease
Compensatory Changes in the Noradrenergic Nervous System in the Locus Ceruleus and Hippocampus of Postmortem Subjects with Alzheimer's Disease and Dementia with Lewy Bodies

Patricia Szot, Sylvia S. White, J. Lynne Greenup, James B. Leverenz, Elaine R. Peskind, and Murray A. Raskind

Northwest Network for Mental Illness Research, Education, and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle, Washington 98108, and Department of Psychiatry and Behavioral Science, University of Washington, Seattle, Washington 98195

In Alzheimer's disease (AD), there is a significant loss of locus ceruleus (LC) noradrenergic neurons. However, functional and anatomical evidence indicates that the remaining noradrenergic neurons may be compensating for the loss. Because the noradrenergic system plays an important role in learning and memory, it is important to determine whether compensation occurs in noradrenergic neurons in the LC and hippocampus of subjects with AD or a related dementing disorder, dementia with Lewy bodies (DLB). We observed profound neuronal loss in the LC in AD and DLB subjects with three major changes in the noradrenergic system consistent with compensation: (1) an increase in tyrosine hydroxylase (TH) mRNA expression in the remaining neurons; (2) sprouting of dendrites into peri-LC dendritic zone, as determined by ₂-adrenoreceptors (ARs) and norepinephrine transporter binding sites; and (3) sprouting of axonal projections to the hippocampus as determined by ₂-ARs. In AD and DLB subjects, the postsynaptic ₁-ARs were normal to elevated. Expression of _1A- and _2A-AR mRNA in the hippocampus of AD and DLB subjects were not altered, but expression of _1D- and _2C-AR mRNA was significantly reduced in the hippocampus of AD and DLB subjects. Therefore, in AD and DLB subjects, there is compensation occurring in the remaining noradrenergic neurons, but there does appear to be a loss of specific AR in the hippocampus. Because changes in these noradrenergic markers in AD versus DLB subjects were similar (except neuronal loss and the increase in TH mRNA were somewhat greater in DLB subjects), the presence of Lewy bodies in addition to plaques and tangles in DLB subjects does not appear to further affect the noradrenergic compensatory changes.

Key words: norepinephrine; Alzheimer's disease; in situ hybridization; adrenoreceptors; locus ceruleus; hippocampus

---

Received Oct 6, 2005; revised November 9, 2005; accepted November 14, 2005.

This article has been cited by other articles:

				F. K. Wiseman Cognitive Enhancement Therapy for a Model of Down Syndrome Science Translational Medicine, November 18, 2009; 1(7): 7ps9 - 7ps9. [Full Text] [PDF]

				E. E. Benarroch The locus ceruleus norepinephrine system: Functional organization and potential clinical significance Neurology, November 17, 2009; 73(20): 1699 - 1704. [Full Text] [PDF]

				J. Brotchie and C. Fitzer-Attas Mechanisms compensating for dopamine loss in early Parkinson disease Neurology, February 17, 2009; 72(7_Supplement_2): S32 - S38. [Abstract] [Full Text] [PDF]

				D. Maysinger, M. Holmes, X. Han, R. M. Epand, E. Pertens, A. Foerster, C. Barlas, D. M. Holtzman, and J. Diamond Ceramide Is Responsible for the Failure of Compensatory Nerve Sprouting in Apolipoprotein E Knock-Out Mice J. Neurosci., July 30, 2008; 28(31): 7891 - 7899. [Abstract] [Full Text] [PDF]

				Y. Zhu, P. Fenik, G. Zhan, E. Mazza, M. Kelz, G. Aston-Jones, and S. C. Veasey Selective Loss of Catecholaminergic Wake Active Neurons in a Murine Sleep Apnea Model J. Neurosci., September 12, 2007; 27(37): 10060 - 10071. [Abstract] [Full Text] [PDF]

				J. L. Whitwell, S. D. Weigand, M. M. Shiung, B. F. Boeve, T. J. Ferman, G. E. Smith, D. S. Knopman, R. C. Petersen, E. E. Benarroch, K. A. Josephs, et al. Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer's disease Brain, March 1, 2007; 130(3): 708 - 719. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help